Encapsulated materials and methods for encapsulating materials

ABSTRACT

A system that incorporates teachings of the present disclosure may include, for example, a method for applying a force to at least one of an inner stream, an outer stream or both of a combined stream to produce a plurality of capsules, receiving image data, processing the image data, detecting undesirable capsules from the processed image data, applying a bias charge only to the detected undesirable capsules, and segregating the biased undesirable capsules from the unbiased desirable capsules. Additional embodiments are disclosed.

PRIOR APPLICATION

This application is a continuation of U.S. patent application Ser. No.12/481,394 filed Jun. 9, 2009, which claims the benefit of priority toU.S. Provisional Application No. 61/060,256 filed Jun. 10, 2008, both ofwhich are incorporated herein by reference in their entirety.

FIELD OF THE DISCLOSURE

The present disclosure relates to the field of materials and materialpreparation or processing. Embodiments of the disclosure relate toencapsulated materials and methods or processes for encapsulatingmaterials such as cellular materials.

BACKGROUND

Cell therapy can depend upon the ability to provide cells to a recipientwhile restraining the recipient's immune response from rejecting thecells. One example of providing these cells has been to provide cellswhile attempting to prohibit the immune response to the cells themselvesand limit the immune response to any associated materials. In the past,attempts have been made to provide encapsulated cells that would protectthe cell from initiating the host's immune response. However, portionsof the cell have often remained exposed, unencapsulated, and/orantigenic. The exposed portions can extend beyond the encapsulate wall,thereby initiating the immune response.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 depicts an illustrative embodiment of an encapsulating apparatus;

FIG. 2 depicts an illustrative embodiment of the apparatus of FIG. 1configured to inspect and segregate capsules;

FIGS. 3-7 depicts illustrative embodiments of capsules created by theapparatus of FIG. 1;

FIG. 8 depicts an illustrative embodiment of the apparatus of FIG. 1 ina laboratory setting; and

FIG. 9 depicts an illustrative diagrammatic representation of a machinein the form of a computer system within which a set of instructions,when executed, may cause the machine to perform any one or more of themethodologies disclosed herein.

DETAILED DESCRIPTION

One embodiment of the present disclosure entails an apparatus having anouter nozzle operable to discharge at an egress of the outer nozzle anouter stream at a first flow rate, the outer stream comprising a shellsolution, and an inner nozzle placed within the outer nozzle, whereinthe inner nozzle is operable to discharge at an egress of the innernozzle an inner stream at a second flow rate, the inner streamcomprising a core solution intermixed with a plurality of materials. Theouter stream can substantially surrounds the inner stream, therebyforming a combined stream. A plurality of capsules can be formedresponsive to a force applied to the combined stream. At least a portionof the plurality of capsules are desirable capsules, each having a coreencapsulated by a portion of the shell solution. The core can have atleast one of the plurality of materials encapsulated by a portion of thecore solution. The at least one material in the core does not protrudean outer surface of the portion of the shell solution.

One embodiment of the present disclosure entails applying a force to acombined stream to produce a plurality of capsules. The combined streamcan have an inner stream with a core solution intermixed with aplurality of materials, and an outer stream of a shell solution. Atleast a portion of the plurality of capsules are desirable capsules,each comprising a core encapsulated by a portion of the shell solution.The core can have at least one of the plurality of materialsencapsulated by a portion of the core solution, whereby the at least onematerial in the core does not protrude an outer surface of the portionof the shell solution.

One embodiment of the present disclosure entails applying a plurality ofcapsules to a patience to reduce or eliminate a disease of the patient.The plurality of capsules can be produced by an apparatus that appliesan acoustic force to a combined stream. The combined stream can have aninner stream including a core solution intermixed with a plurality ofmammalian cells, and an outer stream including a non-antigenic solution.Each of the plurality of capsules can include a core encapsulated by aportion of the non-antigenic solution. The core can have at least one ofthe plurality of mammalian cells encapsulated by a portion of the coresolution, whereby the at least mammalian cell in the core does notprotrude an outer surface of the portion of the non-antigenic solution.

One embodiment of the present disclosure entails producing a pluralityof capsules from a dual stream excited by a force. At least a portion ofthe plurality of capsules are desirable, each having a core surroundedby an outer shell, whereby the core does not protrude an outer surfaceof the outer shell. In one embodiment the core can correspond to amammalian cell.

One embodiment of the present disclosure entails a computer-readablestorage medium having computer instructions to manage operations of theaforementioned apparatus to produce the plurality of capsules accordingto any combination of the foregoing embodiments.

One embodiment of the present disclosure entails a computer-readablestorage medium having computer instructions to direct a device thatapplies the plurality of capsules on a portion of a mammal as medicinaltreatment. The capsules applied to the mammal can have any combinationof the aforementioned embodiments.

The apparatus and methods provided herein will be described withreference to FIGS. 1-9. Referring first to FIG. 1, an apparatus 10 isprovided that includes a coaxial dual-nozzle apparatus 12 orientated inrelation to a receiving reservoir 14. Coaxial dual-nozzle apparatus 12can include an outer nozzle 16 having an inner tube 18 therein.Apparatus 12 can be configured to encapsulate a core within a shell.

Outer nozzle 16 can receive a shell solution 22, and inner nozzle 18 canreceive a core solution 32. Either or both the shell solution 22 andcore solution 32 can be comprised of polymeric or metallic compositionsand can have equal or different concentrations. Core solution 32 cancontain material 20 to be encapsulated such as cells, for example. Theshell and core solutions can comprise a variety of materials dependingon the resulting capsule application including polymers and metals. Uponapplication of forces such as electrostatic, gas dynamic, fluid dynamicand/or acoustic forces of the two solutions, a uniform capsule 26 can beformed at the terminal end of apparatus 12.

In accordance with example implementations, acoustic excitation may beutilized to form capsule 26. Capsule 26 can include material 20surrounded by core 30. Core 30 can also be surrounded by shell 28.Capsule 26 can be produced and provided to reservoir 14. Betweenreservoir 14 and apparatus 12 a power supply can be configured toelectrically charge the capsules exiting the terminal end of apparatus12 and prevent them from coalescing in the receiving reservoir 14, dueto the electrical repulsion between the charged capsules.

Reservoir 14 can be a collection reservoir configured to receive capsule26 within a solution. Reservoir 14 can also be configured to provide anelectrical potential to the solution to prevent or control chargebuild-up in the reservoir. The solution in the reservoir 14 may containadditives to facilitate gelation or crosslinking or solidification ofcapsule 26. Additives can include but are not limited to inorganic saltssuch as CaCl₂ and BaCl₂. According to example implementations material20 may be substantially centered within individual capsule 26 or canmove about the shell 28 without protruding its outer surface.

Material 20 provided to nozzle 18 and eventually encapsulated withincapsule 26 can include biomaterials such as viable or even non-viablebiologic materials including but not limited to mammalian cells such aspancreatic islet cells, myoblast cells, iNOS-expressing cells,parathyroid cells, fibroblast cells, hepatocyte cells, and hormonesecreting cells having a protein base, for example. The islet cells canbe living cells or dormant cells. In example implementations, the cellscan be mammalian and isolated from a variety of donors, including butnot limited to, porcine, ovine, human, and/or bovine.

Within capsule 26, imaging agents can also be provided that can containnanoparticles, for example. In addition, the nanoparticles can beutilized for tracing using imaging technology such as Magnetic ResonanceImaging (MRI). Such additives can be radioactive, have dual modalityand/or be optical or MRI contrast agents, for example. These contrastagents can be inserted into or solidified within an encapsulated portionof capsule 26, for example.

Capsule 26 can include a shell comprising primarily the materialprovided to nozzle 16. The shell and/or the core can be an alginate asalginates can be immuno-inert (non-antigenic), biocompatible, and/orhave limited degradability. In other implementations, the shell and/orcore can comprise a degradable, either fully or partially, material.

In example implementations, the level of cross-linking between thematerials of capsule 26 can be controlled. For example, solution 22 caninclude materials that when capsule 26 is formed the level of bondingand/or interaction between core 30 and shell 28 is predetermined toprovide different strength characteristics. These strengthcharacteristics can include degradation and/or density for example.Other materials can be utilized as the shell portion as well. Theseshell materials can be selected from a variety of materials havingphysical properties necessitated by application requirements. Forexample, carbohydrates, synthetic polymers and the like may be utilizedas well as materials that are compatible under a given set ofapplication conditions.

Utilizing apparatus 10 materials such as cell and/or imaging agents canbe encapsulated and centered to form microcapsules at high productionrates. Example implementations can include encapsulated pancreatic isletcell transplantation where the capsules can be made of alginate and canbe in the range of 450 to 600 μm in diameter. The microcapsuleproduction rate can exceed 1000 microcapsules per second, for example.According to an example implementation, the capsule can include a cellencapsulated by a core 30 which can be in turn surrounded by a shell 28.

One example application of the present disclosure is to provide entirelyencapsulated (i.e., non-antigenic) pancreatic islet cells for thetreatment of Type 1 diabetes without or substantially minimizing the useof immunosuppressive drugs. Although the transplantation of pancreaticislet cells is a viable therapy for Type 1 diabetes the current methodshave limited effectiveness; resulting in poor insulin control andnecessitating the use of immune suppression therapy which restricts thetherapy to a limited number of patients. The encapsulation of isletcells in capsules by prior art systems has been shown to benon-antigenic thus overcoming the limitations of the current technology.

According to example implementations, products of the apparatus andmethods described herein may be applied without the need of immunesuppression. Methods such as those described in K. Y. Jang, K. Kim, andR. S. Upadhye, “Study of sol-gel processing for fabrication of hollowsilica-aerogel spheres,” J. Vac. Sci. Technol. A, 8:33, pp. 1732-1735,1990; K. Kim, K. Y. Jang, and R. S. Upadhye, “Hollow silica spheres ofcontrolled size and porosity by sol-gel processing,” J. Am. Ceram. Soc.,74:8, pp. 1987-1992, 1991; C. Berkland, K. Kim, and D. W. Pack,“Fabrication of PLG microspheres with precisely controlled andmonodisperse size distributions,” J. Controlled Release, 73, 59-74,2001; and Cory Berkland, D. W. Pack, and K. Kim, “Uniform double-walledpolymer microspheres of controllable shell thickness,” Journal ofControlled Release, vol. 96, no. 1, pp. 101-111, 2004, can be applied tothe present disclosure, and the materials utilized therein areincorporated by reference herein.

As an example, the present disclosure provides an apparatus 10 whereinthe inner nozzle 18 can carry an islet cell-containing alginate coresolution 32 of one concentration, and the outer nozzle 16 anotheralginate-containing shell solution 22 of equal or differentconcentrations so that the islet cell-containing core solution stream isat least substantially or completely surrounded by the outer solutionstream to form a coaxial jet. This jet, upon unidirectional oromnidirectional acoustic excitation caused by a common acousticpiezoelectric device, can break up the stream into substantially uniformcore-shell microcapsules with the islet cell-containing alginate coresurrounded by the alginate shell as shown in FIG. 1. By properlyselecting the size of the inner and outer nozzle and adjusting therelative flow rates of the inner and outer solution stream and thefrequency and amplitude of the acoustic excitation, the size andthickness of the capsules may be precisely controlled to the desireddimensions. In this way, one can provide that the islet cells containedin the microcapsules are separated from the microcapsule wall, at leastas much as the thickness of the alginate shell and as a result, theimmunoreactions that may be caused after islet cell transplantation bythe islet cells protruding from the capsules may not be initiated.

According to example implementations, by flowing the solution of theinner nozzle 18 into the outer nozzle 16 to form the shell one canprovide that the cells be contained in the core region of the core-shellmicrocapsules. Material solidification processes (e.g., crosslinking)can start from the outer surface of the microcapsules and move inward toprovide cells that are contained inside the microcapsules away from theouter surface of the microcapsules.

FIG. 2 depicts an illustrative embodiment of the apparatus of FIG. 1configured to inspect and segregate capsules. Utilizing the apparatus,capsules prepared in accordance with the materials and methods describedcan be assayed for completeness of encapsulation. A common highresolution camera 21 can provide images to a controller 25 (e.g., acommon computing device such as a desktop computer or server) which canutilizing common image processing technology to inspect the capsules asthey depart apparatus 10. If a capsule is determined to be anundesirable capsule 24 such as missing a core, or having a protrudingcore, the controller 25 can direct a high voltage source 27 to chargethe undesirable capsule 24 by way of a ring conductor 26 with a negativeor positive bias.

The bias is only applied to undesirable capsules 24. The controller 25can then be programmed to direct a deflection plate 28 to segregate theundesirable capsule 24 away from a path of the desirable capsules 22 byutilizing a potential that draws the undesirable capsule 24 towards theplate 28 and redirects the undesirable capsule 24 to a waste collector29. Since only the undesirable capsules 24 are charged, the desirablecapsules 22 are substantially unaffected by the potential of plate 28,thereby maintaining their current path towards a sample collector 14with a collection solution which may or may not contain additive(s) tofacilitate gelation, crosslinking or solidification.

Referring to FIG. 3, thus fabricated alginate microcapsules are shownthat contain surrogate cells, i.e., ethyl cellulose in the core region.In this illustration, the shell is rigid while the core can move aboutthe capsule without protruding the outer rigid shell. This depiction candemonstrate that these cells in the core do not extend beyond theperimeter established by the microcapsules and thus the presentdisclosure is capable of containing the cells in the core region. Thepresent method can provide control of the polymer concentrations andflow rates of the outer and inner solutions, and thus controlling themass ratios of the two polymers in each nascent droplet, resulting inprecise control of the microcapsule diameter and the shell thickness. Asa result, the minimum distance between the outer surface of themicrocapsule and the cell in the core can be controlled. Likewise, theselection of materials between the inner and outer solutions can bechosen based on porosity of the materials, the porosities giving rise todifferent densities of the materials.

According to example implementations, an ethyl cellulose core, forexample, can be utilized as a surrogate cell using the apparatus 10 ofFIG. 1. Capsules can be produced at a rate of about 1000 per second withalginate as the shell material. A similar feasibility test can also beperformed with a viscous dextran core rather than an ethyl cellulosecore. The capsules produced using the viscouse dextran core with a rigidouter shell is demonstrated in FIG. 4. Microcapsules of the presentdisclosure can be greater than 400 μm in diameter or from about 500 to600 μm in diameter. The cells within the shell can be 20 μm in size witha production rate of about 1000 encapsulated cells per second.

FIGS. 5 and 6 depict optical microscope pictures of alginate capsulesencapsulating mice fibroblast cells (FIG. 5) and bovine liver cells(FIG. 6) with a scale bar of 200 μm. In both illustrations the shellthickness is very thin but rigid, thereby preventing the cells containedtherein from protruding the outer shell. With a thin outer shell, whichcan be produced by a controlled exposure to a solidification solution,the cells in the capsule can move about freely without being overlyconstrained or damaged by an excessively thick rigid shell. FIG. 7depicts optical microscopic pictures of alginate microspheresencapsulating canola oil and water-soluble dextran with a scale bar is200 μm. FIG. 7 illustrates the diversity of microcapsules that can becreated by the apparatus 10 of the present disclosure.

FIG. 8 depicts apparatus 10 in a laboratory setting utilizing anacoustic wave generator. The apparatus depicted in FIG. 8 has beenutilized to produce one or more of the aforementioned capsuleembodiments.

From the foregoing descriptions, it would be evident to an artisan withordinary skill in the art that the aforementioned embodiments can bemodified, reduced, or enhanced without departing from the scope andspirit of the claims described below. For example, apparatus 12 may beconfigured to encapsulate a core within a primarily metal comprisingshell and as such, apparatus 12 may be constructed of materialsconfigured to encapsulate using molten metal. Broadly speaking, therecan be innumerable combinations of materials and shell solutions forproducing capsules by way of the apparatus disclosed herein. Forpractical reasons these embodiments are not disclosed, but arecontemplated by the present disclosure.

Other suitable modifications can be applied to the present disclosure.Accordingly, the reader is directed to the claims for a fullerunderstanding of the breadth and scope of the present disclosure.

FIG. 9 depicts an exemplary diagrammatic representation of a machine inthe form of a computer system 900 within which a set of instructions,when executed, may cause the machine to perform any one or more of themethodologies discussed above. In some embodiments, the machine operatesas a standalone device. In some embodiments, the machine may beconnected (e.g., using a network) to other machines. In a networkeddeployment, the machine may operate in the capacity of a server or aclient user machine in server-client user network environment, or as apeer machine in a peer-to-peer (or distributed) network environment.

The machine may comprise a server computer, a client user computer, apersonal computer (PC), a tablet PC, a laptop computer, a desktopcomputer, a control system, a network router, switch or bridge, or anymachine capable of executing a set of instructions (sequential orotherwise) that specify actions to be taken by that machine. It will beunderstood that a device of the present disclosure includes broadly anyelectronic device that provides voice, video or data communication.Further, while a single machine is illustrated, the term “machine” shallalso be taken to include any collection of machines that individually orjointly execute a set (or multiple sets) of instructions to perform anyone or more of the methodologies discussed herein.

The computer system 900 may include a processor 902 (e.g., a centralprocessing unit (CPU), a graphics processing unit (GPU, or both), a mainmemory 904 and a static memory 906, which communicate with each othervia a bus 908. The computer system 900 may further include a videodisplay unit 910 (e.g., a liquid crystal display (LCD), a flat panel, asolid state display, or a cathode ray tube (CRT)). The computer system900 may include an input device 912 (e.g., a keyboard), a cursor controldevice 914 (e.g., a mouse), a disk drive unit 916, a signal generationdevice 918 (e.g., a speaker or remote control) and a network interfacedevice 920.

The disk drive unit 916 may include a machine-readable medium 922 onwhich is stored one or more sets of instructions (e.g., software 924)embodying any one or more of the methodologies or functions describedherein, including those methods illustrated above. The instructions 924may also reside, completely or at least partially, within the mainmemory 904, the static memory 906, and/or within the processor 902during execution thereof by the computer system 900. The main memory 904and the processor 902 also may constitute machine-readable media.

Dedicated hardware implementations including, but not limited to,application specific integrated circuits, programmable logic arrays andother hardware devices can likewise be constructed to implement themethods described herein. Applications that may include the apparatusand systems of various embodiments broadly include a variety ofelectronic and computer systems. Some embodiments implement functions intwo or more specific interconnected hardware modules or devices withrelated control and data signals communicated between and through themodules, or as portions of an application-specific integrated circuit.Thus, the example system is applicable to software, firmware, andhardware implementations.

In accordance with various embodiments of the present disclosure, themethods described herein are intended for operation as software programsrunning on a computer processor. Furthermore, software implementationscan include, but not limited to, distributed processing orcomponent/object distributed processing, parallel processing, or virtualmachine processing can also be constructed to implement the methodsdescribed herein.

The present disclosure contemplates a machine readable medium containinginstructions 924, or that which receives and executes instructions 924from a propagated signal so that a device connected to a networkenvironment 926 can send or receive voice, video or data, and tocommunicate over the network 926 using the instructions 924. Theinstructions 924 may further be transmitted or received over a network926 via the network interface device 920.

While the machine-readable medium 922 is shown in an example embodimentto be a single medium, the term “machine-readable medium” should betaken to include a single medium or multiple media (e.g., a centralizedor distributed database, and/or associated caches and servers) thatstore the one or more sets of instructions. The term “machine-readablemedium” shall also be taken to include any medium that is capable ofstoring, encoding or carrying a set of instructions for execution by themachine and that cause the machine to perform any one or more of themethodologies of the present disclosure.

The term “machine-readable medium” shall accordingly be taken toinclude, but not be limited to: solid-state memories such as a memorycard or other package that houses one or more read-only (non-volatile)memories, random access memories, or other re-writable (volatile)memories; magneto-optical or optical medium such as a disk or tape; andcarrier wave signals such as a signal embodying computer instructions ina transmission medium; and/or a digital file attachment to e-mail orother self-contained information archive or set of archives isconsidered a distribution medium equivalent to a tangible storagemedium. Accordingly, the disclosure is considered to include any one ormore of a machine-readable medium or a distribution medium, as listedherein and including art-recognized equivalents and successor media, inwhich the software implementations herein are stored.

Although the present specification describes components and functionsimplemented in the embodiments with reference to particular standardsand protocols, the disclosure is not limited to such standards andprotocols. Each of the standards for Internet and other packet switchednetwork transmission (e.g., TCP/IP, UDP/IP, HTML, HTTP) representexamples of the state of the art. Such standards are periodicallysuperseded by faster or more efficient equivalents having essentiallythe same functions. Accordingly, replacement standards and protocolshaving the same functions are considered equivalents.

The illustrations of embodiments described herein are intended toprovide a general understanding of the structure of various embodiments,and they are not intended to serve as a complete description of all theelements and features of apparatus and systems that might make use ofthe structures described herein. Many other embodiments will be apparentto those of skill in the art upon reviewing the above description. Otherembodiments may be utilized and derived therefrom, such that structuraland logical substitutions and changes may be made without departing fromthe scope of this disclosure. Figures are also merely representationaland may not be drawn to scale. Certain proportions thereof may beexaggerated, while others may be minimized. Accordingly, thespecification and drawings are to be regarded in an illustrative ratherthan a restrictive sense.

Such embodiments of the inventive subject matter may be referred toherein, individually and/or collectively, by the term “invention” merelyfor convenience and without intending to voluntarily limit the scope ofthis application to any single invention or inventive concept if morethan one is in fact disclosed. Thus, although specific embodiments havebeen illustrated and described herein, it should be appreciated that anyarrangement calculated to achieve the same purpose may be substitutedfor the specific embodiments shown. This disclosure is intended to coverany and all adaptations or variations of various embodiments.Combinations of the above embodiments, and other embodiments notspecifically described herein, will be apparent to those of skill in theart upon reviewing the above description.

The Abstract of the Disclosure is provided to comply with 37 C.F.R.§1.72(b), requiring an abstract that will allow the reader to quicklyascertain the nature of the technical disclosure. It is submitted withthe understanding that it will not be used to interpret or limit thescope or meaning of the claims. In addition, in the foregoing DetailedDescription, it can be seen that various features are grouped togetherin a single embodiment for the purpose of streamlining the disclosure.This method of disclosure is not to be interpreted as reflecting anintention that the claimed embodiments require more features than areexpressly recited in each claim. Rather, as the following claimsreflect, inventive subject matter lies in less than all features of asingle disclosed embodiment. Thus the following claims are herebyincorporated into the Detailed Description, with each claim standing onits own as a separately claimed subject matter.

1. A method, comprising: applying a force to a combined stream toproduce a plurality of capsules, wherein the combined stream comprisesan inner stream comprising a core solution intermixed with a pluralityof materials, and an outer stream comprising a shell solution, whereinat least a portion of the plurality of capsules are desirable capsules,each comprising a core encapsulated by a portion of the shell solution,wherein the core comprises at least one of the plurality of materialsencapsulated by a portion of the core solution, and wherein the at leastone material in the core does not protrude an outer surface of theportion of the shell solution; detecting undesirable capsules usingimage recognition; applying a bias charge only to the detectedundesirable capsules; and segregating the biased undesirable capsulesfrom the unbiased desirable capsules.
 2. The method of claim 1, whereinthe combined stream comprises a coaxial jet stream
 3. The method ofclaim 1, wherein the force comprises at least one of an acoustic force,an electrostatic force, or a fluid force.
 4. The method of claim 1,wherein the plurality of materials correspond to mammalian cells.
 5. Themethod of claim 1, wherein the plurality of desirable capsules arenon-antigenic.
 6. The method of claim 1, wherein the sensing isperformed by a sensing device.
 7. The method of claim 1, wherein theapplying of the bias charge is performed by a charging device.
 8. Themethod of claim 1, wherein the segregating is performed by a selectiondevice.
 9. The method of claim 1, wherein a size and thickness of theplurality of capsules is controlled by at least one of first and secondflow rates of first and second streams of the combined stream, adiameter of inner and out nozzles used to generate the combined stream,or an amplitude or a magnitude of the force applied to the combinedstream.
 10. The method of claim 1, wherein at least one of the shellsolution or the core solution comprises a biocompatible material. 11.The method of claim 10, wherein the biocompatible material correspondsto an alginate having a non-antigenic property that substantiallyprevents an immune response in a mammal
 12. The method of claim 1,wherein the portion of the shell solution surrounding the core comprisesone of a polymeric solution or an alginate solution.
 13. Acomputer-readable storage medium, comprising instructions which whenexecuted by a processor cause the processor to perform operationscomprising: causing an application device to apply a force to a combinedstream to produce a plurality of capsules, wherein the combined streamcomprises an inner stream comprising a core solution, and an outerstream comprising a shell solution, and wherein at least a portion ofthe plurality of capsules are desirable capsules, each comprising a coreencapsulated by a portion of the shell solution, receiving image datafrom a image sensor; detecting from the image data undesirable capsulesusing image recognition; causing a charging device to apply a biascharge only to the detected undesirable capsules; and causing aselection device to segregate the biased undesirable capsules from theunbiased desirable capsules.
 14. The computer-readable storage medium ofclaim 13, wherein the processor further performs operations comprisingdetecting from the image data the desirable capsules.
 15. Thecomputer-readable storage medium of claim 13, wherein the core isintermixed with a plurality of materials.
 16. The computer-readablestorage medium of claim 15, wherein the plurality of materialscorrespond to a mammalian cell.
 17. The computer-readable storage mediumof claim 16, wherein the mammalian cell corresponds to one of a humancell, a porcine cell, an ovine cell, or a bovine cell.
 18. A method,comprising: applying a force to at least one of an inner stream, anouter stream or both of a combined stream to produce a plurality ofcapsules, wherein the inner stream comprises a core solution intermixedwith a plurality of materials, and the outer stream comprises a shellsolution, wherein at least a portion of the plurality of capsules aredesirable capsules, each comprising a core encapsulated by a portion ofthe shell solution, receiving image data; processing the image data;detecting undesirable capsules from the processed image data; applying abias charge only to the detected undesirable capsules; and segregatingthe biased undesirable capsules from the unbiased desirable capsules.19. The method of claim 18, wherein the plurality of materialscorrespond to a mammalian cell.
 20. The method of claim 19, wherein themammalian cell corresponds to one of a human cell, a porcine cell, anovine cell, or a bovine cell.